Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise.
Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise.
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DOI：
10.1002/cbf.2962
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发表时间：
2013-12
影响因子：
3.6
通讯作者：
Patterson, Cam
中科院分区：
文献类型：
--
作者：
Willis, Monte S.;Min, Jin-Na;Wang, Shaobin;McDonough, Holly;Lockyer, Pamela;Wadosky, Kristine M.;Patterson, Cam
热休克蛋白70相互作用蛋白（CHIP）的羧基端是一种泛素连接酶/辅伴侣，对维持心脏功能至关重要。与野生型对照组相比，缺乏CHIP的小鼠（CHIP-/-）在心脏缺血再灌注损伤后存活率降低，心肌损伤增强，心律失常增加。最近的证据表明，CHIP在分子伴侣辅助的选择性自噬中发挥作用，这是一个与运动诱导的心脏保护相关的过程。为了确定CHIP是否参与心脏自噬，我们用自愿运动挑战CHIP −/−小鼠。CHIP −/−小鼠对运动的反应是增强的自噬反应，这与夸大的心脏肥大表型有关。通过连续5周的超声心动图，CHIP −/−小鼠没有发现功能受损，表明心脏肥大是生理性的，而不是病理性的。进一步确定CHIP在抑制Akt信号传导和自噬中起作用，所述自噬由心肌细胞和完整心脏中的自噬通量确定。总之，心脏CHIP似乎在心脏肥大的发展过程中调节自噬中发挥作用，可能是通过其在支持Akt信号传导中的作用，由体内自愿跑步诱导。
The carboxyl terminus of HSP70-interacting protein (CHIP) is a ubiquitin ligase/co-chaperone critical for the maintenance of cardiac function. Mice lacking CHIP (CHIP −/−) suffer decreased survival, enhanced myocardial injury, and increased arrhythmias compared to wild type controls following challenge with cardiac ischemia reperfusion injury. Recent evidence implicates a role for CHIP in chaperone-assisted selective autophagy, a process that is associated with exercise-induced cardioprotection. To determine whether CHIP is involved in cardiac autophagy, we challenged CHIP −/− mice with voluntary exercise. CHIP −/− mice respond to exercise with an enhanced autophagic response that is associated with an exaggerated cardiac hypertrophy phenotype. No impairment of function was identified in the CHIP −/− mice by serial echocardiography over the five weeks of running, indicating that the cardiac hypertrophy was physiologic not pathologic in nature. It was further determined that CHIP plays a role in inhibiting Akt signaling and autophagy determined by autophagic flux in cardiomyocytes and in the intact heart. Taken together, cardiac CHIP appears to play a role in regulating autophagy during the development of cardiac hypertrophy, possibly by its role in supporting Akt signaling, induced by voluntary running in vivo.
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影响因子：
18.2
作者：
Chen, Ching-Yi;Hsu, Hsiu-Ching;Chen, Ming-Fong
通讯作者：
Chen, Ming-Fong
影响因子：
21.3
作者：
Connell, P;Ballinger, CA;Patterson, C
通讯作者：
Patterson, C
影响因子：
5.6
作者：
Cao, Dian J.;Gillette, Thomas G.;Hill, Joseph A.
通讯作者：
Hill, Joseph A.
影响因子：
2.1
作者：
Golbidi S;Laher I
通讯作者：
Laher I
影响因子：
4.5
作者：
Cuervo, AM;Dice, JF
通讯作者：
Dice, JF